CARDIOVASCULAR EFFECTS OF LONG-TERM ENDOTHELIN INFUSION AND RESPONSESTO ENDOTHELIN DURING ACTH INFUSION IN CONSCIOUS SHEEP

Infusion of endothelin-1 (ET-1) (2000 pmol/h) into conscious sheep for 6 days caused a sustained increase in mean arterial pressure (MAP) of 19 +/- 1 mm Hg. This response was mediated by the vasoconstrictor eff ect of ET-1 and was accompanied by a fall in cardiac output. Plasma re nin concentration fell throughout the infusion and atrial natriuretic peptide was increased on day 1 of ET-1 infusion. Hematocrit dramatical ly increased, probably mainly due to plasma loss resulting from the ET -1-induced increased capillary hydrostatic pressure. To determine whet her increased pressor responsiveness to ET-1 played a role in the rise in MAP caused by corticotropin (ACTH), the responses to bolus doses o f ET-1 were evaluated before ACTH and on days 3 and 5 of ACTH infusion (5 mug/kg/day). ACTH increased MAP from 71 +/- 2 to 87 +/- 3 mm Hg. O n the control day ET-1 (400, 1200, and 2000 pmol) increased MAP by 5 /- 1, 18 +/- 6 and 35 +/- 11 mm Hg, respectively. No initial vasodilat ion occurred. The responses to all doses of ET-1 were similar during A CTH infusion. Plasma levels of ET-1 did not increase during ACTH infus ion. These results demonstrate that long-term infusion of ET-1 caused a sustained increase in blood pressure. There was no evidence that the sensitivity or responsiveness to ET-1 were altered during infusion of ACTH. In conclusion, ET-1 could play a role in the pathogenesis of hy pertension but does not appear to be involved in the increase in blood pressure caused by ACTH.